Normal or low plasma levels of vascular endothelial growth factor (VEGF) have been reported at high altitude (HA), and the effects of acute exercise remain unclear. The effects of sustained hypoxia on plasma leptin levels are controversial, since increased or unchanged plasma leptin was reported at HA compared to sea level (SL) conditions. We assessed the effects of HA on plasma Leptin and VEGF levels at baseline and after maximal exercise in seven healthy subjects (M/F: 5/2, mean age±SD 41.9±13.7 yr). Data were collected at SL and at 5050 m, before and after a maximal incremental exercise test to exhaustion on a stationary cycle ergometer. All subjects completed both tests. Significant differences between SL and HA were observed in maximal power output (SL: 225±83 W, HA: 144±29 W, p<0.01) and VO₂ peak (SL: 2.41±0.67, HA: 1.79±0.35, p<0.001). Plasma leptin at baseline was similar at SL and HA (SL: 7.58±5.42; HA: 7.28±6.7 ng/ml) and showed a nonsignificant trend to decrease after exercise at HA (SL: 6.18±3.24; HA: 4.27±2.62 ng/ml). Plasma VEGF at baseline was much lower at HA than at SL (SL: 131.7±68.9; HA: 40.3±27.5 pg/ml) but did not differ after exercise tests (SL: 138.3±77.9; HA: 115.7±60.1 pg/ml). Therefore, neither hypoxia or acute exercise appeared to affect leptin, while the low plasma VEGF levels at HA at rest suggest that plasma VEGF is not increased by chronic exposure to hypoxia.